期刊
ALZHEIMERS & DEMENTIA
卷 18, 期 1, 页码 65-76出版社
WILEY
DOI: 10.1002/alz.12364
关键词
cortical microstructure; cerebrospinal fluid biomarkers; diffusion; magnetic resonance imaging; neurite orientation dispersion and density imaging; preclinical
资金
- NIH [F30AG059346, R01AG037639, R01AG027161, P30 AG033514]
- Geriatric Research, Education, and Clinical Center of the William S. Middleton Memorial Veterans Hospital
- National Institute of Child Health and Human Development [U54 HD090256]
- BRAIN Initiative [R01EB022883]
- University of Wisconsin Center for Predictive Computational Phenotyping [AI117924]
- National Institutes of Mental Health [R00 MH110596]
- Swedish Research Council [2018-02532, 2017-00915]
- European Research Council [681712]
- Swedish government [ALFGBG-715986, ALFGBG-720931]
- Alzheimer Drug Discovery Foundation (ADDF), USA [201809-2016862, RDAPB-201809-2016615]
- UK Dementia Research Institute at UCL
- Swedish Alzheimer Foundation [AF-742881]
- Hjarnfonden, Sweden [FO2017-0243]
- European Union Joint Program for Neurodegenerative Disorders [JPND2019-466-236]
Neurite orientation dispersion and density imaging (NODDI) is a useful tool for detecting early cortical microstructural alterations in Alzheimer's disease. The interaction between CSF amyloid beta (A beta)(42)/A beta(40) and phosphorylated tau (p-tau) has significant effects on cortical NODDI metrics, demonstrating cortical neurodegenerative changes.
Introduction Neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion-weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment. Methods Using neuroimaging (NODDI and T1-weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys (R) CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (A beta)(42)/A beta(40) and phosphorylated tau (p-tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E epsilon 4. Results We observed a significant CSF A beta(42)/A beta(40) x p-tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. The directionality of these interactive effects indicated: (1) among individuals with lower CSF p-tau, greater amyloid burden was associated with higher cortical NDI; and (2) individuals with greater amyloid and p-tau burden had lower cortical NDI, consistent with cortical neurodegenerative changes. Discussion NDI is a particularly sensitive marker for early cortical changes that occur prior to gross atrophy or development of cognitive impairment.
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